Engineering Biomaterials to Influence Oligodendroglial Growth, Maturation, and Myelin Production

Abstract

Millions of people suffer from damage or disease to the nervous system that results in a loss of myelin, such as through a spinal cord injury or multiple sclerosis. Diminished myelin levels lead to further cell death in which unmyelinated neurons die. In the central nervous system, a loss of myelin is especially detrimental because of its poor ability to regenerate. Cell therapies such as stem or precursor cell injection have been investigated as stem cells are able to grow and differentiate into the damaged cells; however, stem cell injection alone has been unsuccessful in many areas of neural regeneration. Therefore, researchers have begun exploring combined therapies with biomaterials that promote cell growth and differentiation while localizing cells in the injured area. The regrowth of myelinating oligodendrocytes from neural stem cells through a biomaterials approach may prove to be a beneficial strategy following the onset of demyelination. This article reviews recent advancements in biomaterial strategies for the differentiation of neural stem cells into oligodendrocytes, and presents new data indicating appropriate properties for oligodendrocyte precursor cell growth. In some cases, an increase in oligodendrocyte differentiation alongside neurons is further highlighted for functional improvements where the biomaterial was then tested for increased myelination both in vitro and in vivo.

Polyethylene glycol in spinal cord injury repair: a critical review

“…Compared to long-chain-length PEG, hydrogels derived from shorter-chain-length PEGs possessed a higher cross-linking density that resulted in a stiffer material and led to higher expressions of PDGFRα. 52 These studies reinforce the importance of modulating mechanical properties to fit the differentiating neural 53 , 54 or glial cells 55 , 56 for treating SCI.…”

Particles Containing Cells as a Strategy to Promote Remyelination in Patients With Multiple Sclerosis

“…OPCs clearly merit consideration as a therapeutic option targeting remyelination in MS, with the delivery of exogenous OPCs to demyelinated areas; however, there remain several outstanding issues (66). Many of these are addressed in an extensive review published recently by Unal et al (67).…”

3D Hyaluronic Acid Hydrogels for Modeling Oligodendrocyte Progenitor Cell Behavior as a Function of Matrix Stiffness

“…18 Hydrogel cell culture models enable interrogation of the roles that extracellular cues such as matrix stiffness play in regulating salient cell behaviors. 10,[19][20][21] Jagielska et al showed that OPCs are mechanosensitive, with proliferation being greatest on 2D substrates with Young's elastic moduli of 700 Pa. 22 3D culture systems offer the potential to study cell-cell and cell-matrix interactions as well as biotransport conditions in a more physiologically-relevant setting. We previously showed that OPC metabolic activity was greatest within 3D PEG hydrogels with storage moduli of 240 ± 84 Pa in comparison to 630 ± 79 Pa. 23 In this work, we used 3D HA hydrogels to interrogate the effects of stiffness and mesh size on OPC proliferation, metabolic activity, and spheroid volume.…”